Melanoma is the deadliest form of skin cancer, and its incidence is on the rise (1-3). Treatment options for advanced melanoma are limited and rarely curative. While 5 year survival for stage III melanoma patients can reach up to 69% depending on the patient subcategory, the reported survival for stage IV disease is rarely longer than a year (3). Although long-term survival for patients with advanced melanoma is low despite currently available therapies, some patients can survive for prolonged periods with metastatic disease. The ability to predict survival in metastatic melanoma with greater accuracy could improve current treatment decisions and aid in the design of new therapies that might be tailored to specific subgroups of patients. The majority of innovative and improved prediction models, however, are geared toward evaluating the metastatic potential of primary tumors, as opposed to evaluating the progression potential of metastatic disease. It would potentially be useful to biologically subclassify melanoma that has already metastasized, beyond the use of the conventional Tumor, Node, Metastasis (TNM) staging, into categories that more accurately predict patient survival (4).
Many studies have shown the importance of the immune response in the equilibrium state of primary neoplasia but very few evidenced its importance in managing metastasis [Piras et al. (2005) Cancer 104: 1246-1254]. Both predictive potential and novelty of findings especially associated with immune regulation as well as proliferation suggest necessity of further development of this approach [Francken et al. (2004) Ann Surg Oncol 11: 426-433]. Presence of leukocytes within the lesions as an easy and highly predictive tool of patient prognosis has not been sufficiently explored, possibly due to the conflicting studies that show both beneficial and detrimental effects [Piras et al. (2005) Cancer 104: 1246-1254; Sato et al. (2005) Proc Natl Acad Sci USA 102: 18538-18543; Galon et al. (2006) Science 313: 1960-1964]. Establishing evidence of inflammation at the molecular and cellular level in the lesions is crucial for advancement of immunotherapies in melanoma. There is a need to characterize in detail the immune regulatory molecules that are associated with the increased survival since immunotherapy could be utilized to further boost an already beneficial molecular sub profile.
The citation of references herein shall not be construed as an admission that such is prior art to the present invention.